Type II pleuropulmonary blastoma mistaken for rhabdomyosarcoma: A case report

Abstract

Introduction

Pleuropulmonary blastoma (PPB) is rare, representing 0.3 % of all pediatric cancers. PPB is classified into three subtypes and may progress from type I to types II and III, with a worse prognosis. Given its rarity, the diagnosis is frequently challenging.

Case presentation

We report an occurrence of PPB in a 3-year-old girl, who presented recurrent pneumopathy. Imaging investigations revealed a large solid lesion in the left hemithorax. Biopsy followed by histological analysis suggested rhabdomyosarcoma. The patient received neoadjuvant chemotherapy before proceeding to complete tumor excision. Surgical exploration revealed that the tumor was primitively related to parietal pleura and lower lobe of left lung. Histopathology of the tumor retained a definitive diagnosis of PPB type II. Postoperative course was uneventful, and a cerebral MRI ruled out brain metastasis. Adjuvant chemotherapy was administered.

Discussion

Clinical expression of PPB is nonspecific and variable. It ranges from a dry cough to respiratory distress. Standard radiography is the first examination to perform and CT is the gold standard for characterization thoracic masses. Surgery and chemotherapy are the pillars of treatment. Indications depend on the tumor type, its extent and its resectability.

Conclusion

PPB is an aggressive tumor that occurs only in children. Due to the rarity of PPB, evidence on optimal treatment is still insufficient. Careful follow-up is necessary searching for local recurrence or metastasis.

Highlights

• •Pleuropulmonary blastoma is a rare and aggressive tumour that exclusively affects children
• •Histologically, due to the presence of rhabdomyoblastic features, particularly in Pleuropulmonary blastoma, type III, Pleuropulmonary blastoma, previously was thought to represent a rhabdomyosarcoma of the lung
• •Pathological confirmation is crucial for accurate diagnosis and appropriate treatment planning.
• •Surgery and chemotherapy are the mainstay of treatment, the optimal approach is not well-established due to the rarity of this tumor.

1. Introduction

Pleuropulmonary blastoma (PPB) is a rare and aggressive tumor that exclusively affects children [1]. Histologically, PPB includes a combination of blastoma and mesenchymal components with no malignant epithelial tissue. We can distinguish 3 types of PPB based on morphology of the tumor: type I purely cystic, type II cystic and solid tumor and type III purely solid [2]. Progression from type I to type II then III is possible, which is a particularity of PPB. The incidence of progression has been reported to be approximately 10 % [3]. The diagnostic and therapeutic management of PPB remains challenging given its rarity, unspecific clinical presentation and severe prognosis. Here, we report a case of PPB in a 3 years old girl who presented with a one-month history of recurrent pneumopathies. Our work is reported in accordance with the SCARE criteria [4]. Our aim was to highlight the diagnostic difficulties of PPB for both clinicians and pathologists.

2. Case report

A 3-year-old girl who had been experiencing non-improving respiratory tract symptoms: non-productive cough, for one month, and recurrent bronchial infections, despite receiving symptomatic treatment and antibiotics. There was no significant family history. The patient had no underlying medical illness and there was no prenatal diagnosis of lung mass or malformation. Physical examination revealed an altered general state with an absence of breath sounds on the left lung bas, and the patient's oxygen saturation was 87 % on room air. There were no focal neurological deficits or fever. A Chest X-ray showed an opaque mass in the left lung with contralateral medistinal deviation (Fig. 1). A chest computed tomography (CT) scan was performed, revealing a large, mass that almost completely occupied the left hemithorax, and displaced the mediastinum to the right. There was a pleural effusion but no evidence of costal erosion or diaphragm invasion (Fig. 2). Scan-guided needle biopsy was performed and followed by a histological analysis suggested rhabdomyosarcoma (RMS). The remaining staging ruled out other tumor localizations. The patient received 4 cycles of neoadjuvant chemotherapy IVA (ifosfamide, vincristine, and dactinomycin), which resulted in a satisfying response, as evidenced by a 75 % reduction in the mass observed in the control chest CT (Fig. 3). Surgical exploration, through an open left thoracotomy, revealed that the tumor was primarily related to parietal pleura and lower lobe of left lung occupying its quarter. Careful mobilization of the tumor through the fifth intercostal space was performed. En-bloc wedge resection was possible, without needing the entire lobe resection. The tumor was macroscopically completely resected, including parietal pleura from the thoracic wall. The surgical specimen weighed 49 g and measured 9x5x3 cm, appearing both solid and cystic upon sectioning. The solid areas had a brain-like appearance, while the necrotic areas were whitish in color (Fig. 4A). The final histological examination of two entire slices indicated the presence of a viable malignant tumor proliferation at 60 %, comprising two cystic and solid components. The sarcomatous component was of rhabdomyosarcomatous and chondrosarcomatous types. The definitive diagnosis was confirmed as type II PPB, which was completely removed (Fig. 4B).

Fig. 1.

Chest Radiograph showing a radio-opaque mass lesion occupying the left hemithorax with controlatéral mediastinal deviation.

Fig. 2.

A - Axial chest CT mediastinal window with contrast enhancement.

B - Coronal chest CT mediastinal window with contrast enhancement.

C - Sagittal chest CT mediastinal window with contrast enhancement.

Large well defined solid mass with heterogeneous enhancement occupying almost the totality of the left hemi-thorax with controlateral mediastinum deviation and no evidence of parietal invasion. The Sagittal reformed image shows the associated pleural effusion.

Fig. 3.

Chest CT after 4 cycles of neoadjuvant chemotherapy IVA.

A- Axial chest CT mediastinal window with contrast enhancement.

B- Axial chest CT Lung window.

C- Sagittal chest CT Lung window.

Decrease in size of the left pleural-pulmonary tissue mass with secondary appearance of excavations with aerated content.

Fig. 4.

A/ Gross examination of a type II pleuropulmonary blastoma presenting as a solid-cystic lesion in the lung of a 3-year-old girl; B/ Type II pleuropulmonary blastoma tumor composed of cystic and solid components (H&E ×200): The cystic component (asterix) is composed of cysts separated by fibrous septa of varying thickness and lined by alveolar-type epithelium. Beneath this lining, there was a condensation of immature mesenchymal cells, often associated with varying numbers of rhabdomyoblasts (head arrow). The solid component consisted of a mixture of blastemal and sarcomatous foci. The sarcomatous component was of rhabdomyosarcomatous and chondrosarcomatous types (arrow).

The postoperative course was uneventful, and a cerebral MRI ruled out brain metastasis. Adjuvant chemotherapy was administered (ifosfamide, vincristine, actinomycin D, and doxorubicin), and was well tolerated. A follow-up chest CT scan confirmed the absence of tumor residue and complete regression of the pleural effusion (Fig. 5). Due to lack of funds, the patient was not tested for DICER1 gene mutations.

Fig. 5.

Post-tumorectomy chest CT control.

A- Axial chest CT mediastinal window with contrast enhancement.

B- Axial chest CT Lung window.

C- Sagittal chest CT Lung window.

No evidence of tumor residue and complete regression of the pleural effusion.

3. Discussion

The occurrence of primary pulmonary tumors in children is rare, accounting for only 0.3 % of all pediatric cancers [5]. Among the primary pulmonary malignancies, metastatic lesions are the most frequently encountered in children [1]. Metastatic lung tumors in children are more likely to originate from Wilm's tumor or osteosarcoma than other types of cancer, such us RMS, hepatocellular carcinoma, hepatoblastoma, or Ewing's sarcoma [1].

Primary pulmonary malignancies in children are uncommon, and PPB represents <1 % of these cases [6]. PPB was first described by Manivel et al. in 1988 [7]. In 1997, Priest et al. classified PPB into three types based on its histological features: cystic tumor (type I), mixed cystic and solid tumor (type II), and pure solid tumor (type III) [8]. Type I PPB has the best prognosis among the three types, with a 5-year disease-free survival rate of 80–90 %. It is important to note that all reported deaths associated with type I occurred with progression to type II or III, further emphasizing the importance of early detection and treatment [3].

Histologically, PPB is characterized by a mixture of blastemal islands with high mitotic activity and areas of undifferentiated loose mesenchymal spindle cells. Initially, due to the presence of rhabdomyoblastic features, particularly in PPB type III, PPB was thought to represent a RMS of the lung [9], [10].

PPB remains the most well-known DICER1-related malignant tumor, up to 80 % of patients with PBP carrying a DICER1 mutation [11]. DICER1 mutations have been associated with an increased risk of several other types of tumors, including genitourinary embryonal RMS, Wilms tumor, anaplastic sarcoma of the kidney, Sertoli-Leydig cell tumors of the ovary, and others [10]. The wide spectrum of associated tumors underscores the importance of recognizing DICER1 syndrome in pediatric patients with unusual or multiple tumor types. Screening for DICER1 mutations does not have prognostic value [11], [12].

PPB typically occurs in young children, with type I occurring in children younger than 3 years old, type II occurring in children aged 3 to 6 years, and type III occurring in children older than 6 years [2]. However, there have been a few reported cases of PPB in adolescence and young adulthood [3], [13], [14].

According to the literature, there have only been five reported cases of prenatal diagnosis, making it an exceptionally uncommon occurrence [15].

The way PPB manifests clinically is not specific and can differ significantly. Symptoms can vary from a dry cough to respiratory distress. Non-productive cough as presenting in our case was reported by Bownes et al. [3]. Increasing breathlessness and respiratory distress were respectively reported [6], [14].

If a patient experience recurring upper respiratory tract infections that do not respond to initial treatment, it could indicate the possibility of PPB. It is worth noting that PPB may be discovered unintentionally [16].

Standard radiography is the initial examination performed to investigate respiratory symptoms and can lead to the discovery of these tumors. This imaging technique typically reveals a large opacity, accompanied by a contralateral mediastinal deviation. Due to its significant size, determining the origin of this opacity can be challenging. X-rays may also reveal the presence of a liquid pleural effusion, pneumothorax, or hydropneumothorax [16].

CT is considered the gold standard for characterizing thoracic masses. The appearance of the mass on CT varies depending on the type of tumor [6]: Type I tumors present as uni or multilocular cystic masses with air present within the cysts. Type II tumors appear as multilocular masses with solid portions, and Type III tumors appear as solid masses with a varied density and enhancement. PPB only shows distant metastasis in association with types II and III, and it has a propensity to metastasize to the brain, medullary spinal cord, and bone [15].

PPB can display a variety of mesenchymal components, and may show differentiation into cartilage, rhabdomyoblasts, or fibroblasts. In the current case, the biopsy might have only captured a portion of the mesenchymal component of the tumor, leading to an incorrect diagnosis of RMS. While Immunohistochemical staining (IHC) may not have much diagnostic value in pleuropulmonary blastoma, the diagnosis can be made based on histopathological examination alone [17]. In the case of type II and type III PPB, differential diagnosis often includes solid tumors that are commonly seen in pediatric patients, such as neuroblastoma, Ewing's sarcoma, RMS, and inflammatory myofibroblastic tumor. Infantile fibrosarcoma is another potential differential diagnosis, but this type of tumor exclusively occurs in neonates and infants [18]. The mainstays of treatment for PPB are surgery and chemotherapy, and the indications for each depend on the tumor type, extent, and resectability. Radical surgical resection is essential, and may include cystectomy, segmentectomy, lobectomy, or pneumonectomy. For patients with type I PPB, surgical resection alone can be curative, but adjuvant chemotherapy should be added if there is tumor spill, incomplete resection, or local invasion of adjacent structures [19]. Patient with type II and type III PPB, require both systemic chemotherapy and surgical resection. In cases of large type II or III PPB with extensive pleural spread, extrapleural pneumonectomy may be required to achieve local control. Neoadjuvant chemotherapy can be used to optimize local control with radical surgery for large tumors exceeding 10 cm [20]. In the present case, neoadjuvant chemotherapy was used to minimize the radical surgical approach, so local control was achieved with simple wedge resection. Systemic chemotherapy is recommended for patients with types II or III PPB, and the regimen includes Ifosfamide, Vincristine, Actinomycin-D, and Doxorubicin [3]. There has been no demonstrated benefit of radiation therapy for patients with unresectable residual primary tumors [3].

4. Conclusion

Our case highlights the importance of correctly diagnosing PPB, a rare malignant tumor in children with variable clinical and radiological presentations that can mimic other solid tumors. Pathological confirmation is crucial for accurate diagnosis and appropriate treatment planning. Although surgery and chemotherapy are the mainstay of treatment, the optimal approach is not well-established due to the rarity of this tumor. Therefore, more research is needed to determine the best management strategies for PPB.

Consent

Written informed consent was obtained from the patient's parents/legal guardian for publication of this case report and accompanying images.

Ethical approval

Ethical approval was given by Charles Nicolle Teaching Hospital Ethics Committee, Tunis, Tunisia.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contribution

Karray Amina: concept or design, data collection, data analysis, writing the paper.

Boussetta Abir: concept or design, writing the paper.

Sassi Farah: writing and data collection.

Cherifi Walid: writing and data collection.

Haouat Slim: data collection.

Gargah Tahar: proofreading.

Guarantor

Dr. Amina Karray.

Research registration number

Not applicable.

Declaration of competing interest

The authors declare that there are no conflicts of interest regarding the publication of this article.